Today we shift the format of our Conversations with Giants in Medicine and allow three of our most charismatic giants (Robert Lefkowitz, Joseph Goldstein, and Michael Brown) to interview each other (Figure 1). Lefkowitz (Duke University) is known for his seminal discoveries in understanding G protein–coupled receptor function. The legendary partnership between Brown and Goldstein (University of Texas Southwestern Medical Center) has spanned four decades. Together they were awarded the 1985 Nobel Prize in Physiology or Medicine acknowledging their discovery of the LDL cholesterol receptor and its role in the regulation of cholesterol metabolism. The full interview can be seen on the JCI website, http://www. jci. org/kiosk/cgm. Lefkowitz: I’m delighted to be here, particularly with two very close friends and colleagues who have always been scientific heroes of mine. I want to speak a little about our upbringing, since it is a little different for all of us. I grew up in the Bronx and first developed an interest in becoming a physician when I was in the third grade, inspired by my family physician, who just captivated me. How did you both get started? Goldstein: I was brought up in a town called Kingstree, South Carolina, that had about maybe 3,500 people. I went to a high school that had 60 students. In those days, there was complete segregation. It was an all-white high school, but I had really good teachers who focused on reading, writing, and arithmetic. And I had a great chemistry teacher. I guess that my first real interest in science was chemistry in high school. Brown: I was born in Brooklyn. My motivation for medicine came from my father. He kept telling me that the only person who doesn’t have a boss is a doctor. And in his community, the doctors were the highest, the most respected people. And in high school, I became an amateur radio operator building transmitters and receivers. And so, in the middle of the night, plugging it in and blowing every fuse in the house, and then you had to go back and sort of retrace your steps and figure out where you went wrong. And that’s basically what I’ve done ever since in the lab.